Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab
Bevacizumab (Bev) is a humanized vascular endothelial growth factor monoclonal antibody that is used with chemotherapeutic drugs for the treatment of metastatic colorectal cancer (mCRC). Bev-induced hypertension (HT) is the most common adverse reaction during clinical practice. However, at present,...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.829059/full |
| _version_ | 1818237204510539776 |
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| author | Tianshu Ren Tianshu Ren Hui Jia Qiong Wu Yan Zhang Qun Ma Dong Yao Xudong Gao Danni Xie Zihua Xu Qingchun Zhao Qingchun Zhao Yingshi Zhang |
| author_facet | Tianshu Ren Tianshu Ren Hui Jia Qiong Wu Yan Zhang Qun Ma Dong Yao Xudong Gao Danni Xie Zihua Xu Qingchun Zhao Qingchun Zhao Yingshi Zhang |
| author_sort | Tianshu Ren |
| collection | DOAJ |
| description | Bevacizumab (Bev) is a humanized vascular endothelial growth factor monoclonal antibody that is used with chemotherapeutic drugs for the treatment of metastatic colorectal cancer (mCRC). Bev-induced hypertension (HT) is the most common adverse reaction during clinical practice. However, at present, appropriate antihypertensive agents for Bev-induced HT are unavailable. In this study, retrospective analysis of clinical data from mCRC patients who received renin-angiotensin system inhibitors (RASIs) showed significant survival benefits of overall survival (OS) and progression-free survival (PFS) over patients who received calcium channel blockers (CCBs) and patients who received no antihypertensive drug (NO: Y2020046 retrospectively registered). An experiment of HCT116 colon cancer cell xenografts in mice confirmed that combined treatment of Bev and lisinopril (Lis), a RASI, synergistically inhibited subcutaneous tumor growth and enhanced the concentration of 5-fluorouracil (5-Fu) in tumor tissues. Our results showed that the addition of Lis did not interfere with the vascular normalization effect promoted by Bev, but also inhibited collagen and hyaluronic acid (HA) deposition and significantly downregulated the expression of TGF-β1 and downstream SMAD signaling components which were enhanced by Bev, ultimately remodeling primary extracellular matrix components. In conclusion, RASIs and Bev have synergistic effect in the treatment of colorectal cancer and RASIs might be an optimal choice for the treatment of Bev-induced HT. |
| first_indexed | 2024-12-12T12:22:03Z |
| format | Article |
| id | doaj.art-a9be20ef6f484508970e657a911f252a |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T12:22:03Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a9be20ef6f484508970e657a911f252a2022-12-22T00:24:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.829059829059Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and BevacizumabTianshu Ren0Tianshu Ren1Hui Jia2Qiong Wu3Yan Zhang4Qun Ma5Dong Yao6Xudong Gao7Danni Xie8Zihua Xu9Qingchun Zhao10Qingchun Zhao11Yingshi Zhang12Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, ChinaDepartment of Pharmacy, General Hospital of Northern Theater Command, Shenyang, ChinaDepartment of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, ChinaBevacizumab (Bev) is a humanized vascular endothelial growth factor monoclonal antibody that is used with chemotherapeutic drugs for the treatment of metastatic colorectal cancer (mCRC). Bev-induced hypertension (HT) is the most common adverse reaction during clinical practice. However, at present, appropriate antihypertensive agents for Bev-induced HT are unavailable. In this study, retrospective analysis of clinical data from mCRC patients who received renin-angiotensin system inhibitors (RASIs) showed significant survival benefits of overall survival (OS) and progression-free survival (PFS) over patients who received calcium channel blockers (CCBs) and patients who received no antihypertensive drug (NO: Y2020046 retrospectively registered). An experiment of HCT116 colon cancer cell xenografts in mice confirmed that combined treatment of Bev and lisinopril (Lis), a RASI, synergistically inhibited subcutaneous tumor growth and enhanced the concentration of 5-fluorouracil (5-Fu) in tumor tissues. Our results showed that the addition of Lis did not interfere with the vascular normalization effect promoted by Bev, but also inhibited collagen and hyaluronic acid (HA) deposition and significantly downregulated the expression of TGF-β1 and downstream SMAD signaling components which were enhanced by Bev, ultimately remodeling primary extracellular matrix components. In conclusion, RASIs and Bev have synergistic effect in the treatment of colorectal cancer and RASIs might be an optimal choice for the treatment of Bev-induced HT.https://www.frontiersin.org/articles/10.3389/fonc.2022.829059/fullbevacizumabrenin-angiotensin system inhibitorshypertensionangiogenesisextracellular matrix components |
| spellingShingle | Tianshu Ren Tianshu Ren Hui Jia Qiong Wu Yan Zhang Qun Ma Dong Yao Xudong Gao Danni Xie Zihua Xu Qingchun Zhao Qingchun Zhao Yingshi Zhang Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab Frontiers in Oncology bevacizumab renin-angiotensin system inhibitors hypertension angiogenesis extracellular matrix components |
| title | Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab |
| title_full | Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab |
| title_fullStr | Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab |
| title_full_unstemmed | Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab |
| title_short | Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab |
| title_sort | inhibition of angiogenesis and extracellular matrix remodeling synergistic effect of renin angiotensin system inhibitors and bevacizumab |
| topic | bevacizumab renin-angiotensin system inhibitors hypertension angiogenesis extracellular matrix components |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.829059/full |
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